The long-term goal of this project is to develop a non- radioactive homogeneous assay suitable for studying macromolecular interactions. The assay would be a widely applicable technique useful in research, diagnostic, and drug discovery. Recent proliferation of combinatorial chemistry techniques has mad libraries increasingly larger, inexpensive, and tailored to specific application. The ability to rapidly identify antagonistic compounds has importance in fields as diverse as basic research, diagnostics, and drug screening. Currently no homogeneous, non-radioactive technique exists which is suited to a range of macromolecular types and interactions. The proposed colloidal silver aggregation assay format meets this need by providing a fast optical readout regarding interaction between two ligands. Preliminary studies have used model systems to demonstrate the feasibility of this technology. These studies reveal the need for an organic monolayer on the metal to provide macromolecular coupling sites and protect ligand from direct metal contact. Our specific aims for Phase I are to construct and characterize colloid monolayers, assess aggregation using covalently coupled ligands and explore various functional parameters of such an assay. Completion of this research will result in a novel high-through put assay for ligand interactions capable of identifying compounds which affect binding. PROPOSED COMMERCIAL APPLICATIONS: This research may result in the development of a novel, homogeneous, optical assay for use in identifying inhibitors of ligand interactions.